Abstract
Purpose: :
To develop an animal model of optic neuritis and to investigate the relationship between size of demyelinated lesion, extent of axonal loss and degree of latency delay in visual evoked potentials (VEPs).
Methods: :
Varying doses (0.4~0.8 µl) of lysolecithin (1%) were microinjected into one optic nerve, 2 mm posterior to the globe in 8 SD rats. Fellow eyes served as controls. Flash VEPs were recorded using a mini-Ganzfeld stimulator (3 cd.s/m2) and skull implanted screw electrodes. VEP recordings were performed at day 0, 2, 4 and 6. Animals were then sacrificed and perfused. The optic nerves were stained with Luxol-fast blue and Bielschowsky’s silver impregnation to assess demyelination and axonal pathology respectively. Demyelinated areas were measured on serial sections (every 250 µm) and lesion volumes were deduced. Mean axonal density was calculated for each nerve by counting the number of axons in 9 standardized fields of 400 µm 2.
Results: :
Partial lesions of demyelination (0% to 95% of the cross sectional area) and variable axonal loss were induced. The injected eye showed a significant latency delay and amplitude decrease in the VEPs. The mean latencies of P1, N1and P2 increased from 27.08±1.55 ms to 33.35±2.75 ms (p=0.03), 41.5±1.87 ms to 52.7±3.51 ms (p=0.02) and 61.05±2.31 ms to 80.38±4.19 ms (p=0.01) respectively. The mean amplitudes of P1-N1 and N1-P2 decreased from 28.96±2.22 µV to 12.32±2.85 µV (p<0.001) and 44.52±3.28 µV to 24.59±4.71 µV (p=0.01). The mean density of axons was 20.18±2.62×104/mm2 in the demyelinated nerves and 35.53±3.29×104/mm2 in the controls. Regression analysis demonstrated a strong correlation between N1 latency delay and the volume of demyelinated lesion (R2=0.82, p=0.002) but not with axonal loss (R2=0.38, p=0.104), and a positive linear association between N1-P2 amplitude decrease and the axonal loss (R2=0.59, p=0.027).
Conclusions: :
The latency of the VEP accurately reflected the amount of demyelination in the visual pathway, and loss of amplitude correlated with axonal damage in this animal model. The VEP provides an inexpensive and highly sensitive tool to measure de/remyelination in vivo. This supports its role in evaluating the prognosis of optic neuritis and potentially investigating new remyelinating therapies.
Keywords: optic nerve • electrophysiology: non-clinical • neuro-ophthalmology: optic nerve